CG0070 + Nivolumab for Bladder Cancer

Overseen By Austin Lannon

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immune checkpoint inhibitors, Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, Cardiac diseases, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for muscle-invasive bladder cancer, specifically for those unable to use the common chemotherapy drug cisplatin. The trial combines CG0070, delivered directly into the bladder, with Nivolumab, an intravenous medication. Researchers aim to determine if this combination is safe and effective in shrinking tumors before surgery. Suitable participants have bladder cancer that invades muscle and cannot take cisplatin due to health issues like kidney problems or hearing loss. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take immunosuppressive agents within 14 days of starting the study treatment, and certain antiviral medications must be stopped 14 days before and after CG0070 treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of CG0070 and Nivolumab is under study for safety in treating muscle-invasive bladder cancer. Previous studies have found that this combination is generally well-tolerated. For example, a study published in *Nature Medicine* found that this treatment was safe for patients unable to take cisplatin, a common chemotherapy drug.

Most patients handled the treatment without serious side effects. While some side effects occurred, they were mostly mild to moderate. These findings suggest that the treatment may be safe for people with muscle-invasive bladder cancer. However, ongoing research aims to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CG0070 and Nivolumab for bladder cancer because these treatments offer a novel approach compared to traditional therapies like chemotherapy or surgery. CG0070 is an oncolytic virus that selectively targets and destroys cancer cells, which is a different mechanism than typical treatments. Nivolumab, an immunotherapy, works by boosting the body's immune response against cancer cells, offering a potential advantage in fighting the disease more effectively. This combination targets cancer in a unique way, potentially leading to improved outcomes for patients with bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that the combination of CG0070 and Nivolumab, which participants in this trial will receive, holds promise for treating muscle-invasive bladder cancer, particularly for patients unable to receive cisplatin. Previous studies found that this treatment led to a complete response in 42.1% of patients, meaning the cancer was not detectable after treatment in nearly half of them. The treatment targets cancer cells while sparing normal ones, making it both safe and effective. Early findings suggest this could be a strong option for those who can't use standard chemotherapy. ^{1 2 4 5 6}

Who Is on the Research Team?

Roger Li, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Muscle Invasive Bladder Cancer (MIBC) who can't have cisplatin chemotherapy due to poor kidney function, hearing loss, neuropathy, heart failure or personal choice. They must be fit for certain bladder surgeries and willing to provide tissue samples. Pregnant women, those with serious medical conditions or allergies to the drugs, prior immune therapy use or other active cancers are excluded.

Inclusion Criteria

My bladder cancer is confirmed and falls within specific stages without distant spread.

My bladder cancer surgery was within the last 3 months, and there's enough tissue for testing.

Exclusion Criteria

I have bladder cancer symptoms that may prevent me from completing the treatment.

I have been diagnosed with HIV.

I have not had any autoimmune diseases except for well-controlled conditions like type 1 diabetes or eczema in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical CG0070 (6 instillations) and IV Nivolumab (2 doses) as neoadjuvant therapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• CG0070
• Nivolumab

Trial Overview The study tests a combination of CG0070 (a drug put directly into the bladder) and Nivolumab (an IV drug), in patients not eligible for standard chemotherapy. It aims to assess how safe this combo is and how well it works before removing the bladder.

How Is the Trial Designed?

Group I: Participants Receiving CG0070 & Nivolumab Experimental Treatment 2 Interventions

Both CG0070 (x 6 instillations) and nivolumab (x 2 doses) will be administered at their single-agent dose and schedule.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

CG Oncology, Inc.

Industry Sponsor

Trials

9

Recruited

900+

Richard M. Shulze Family Foundation

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

Immunotherapy, particularly immune checkpoint inhibitors like atezolizumab and nivolumab, has received accelerated FDA approval for treating metastatic urothelial carcinoma, showing promise in improving patient outcomes.

The use of immunotherapy can lead to unique immune-related adverse events and response patterns, such as pseudoprogression, highlighting the need for careful management and the potential for predictive biomarkers to identify patients who will benefit most from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. Siefker-Radtke, A., Curti, B.[2021]

Intravesical immunotherapy with Bacillus Calmette-Guérin remains the standard treatment for non-muscle invasive urothelial bladder cancer (UBC), but recent advances in checkpoint blockade immunotherapy targeting PD-1 and PD-L1 have shown promise for patients with advanced UBC, leading to the FDA approval of five checkpoint inhibitors in the last two years.

The effectiveness of these immunotherapies highlights the importance of understanding the complex interactions between cancer cells and the immune system, as well as the potential for genomic markers to predict patient responses to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. Cheng, W., Fu, D., Xu, F., et al.[2020]

Avelumab, an antibody targeting PD-L1, showed significant antitumor effects in a bladder cancer model, indicating its potential as an effective treatment for non-muscle invasive urothelial carcinoma.

The study found that the antitumor effects of avelumab were more reliant on CD4 T cells rather than CD8 T cells, suggesting that enhancing the adaptive immune response could improve treatment outcomes for bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. Vandeveer, AJ., Fallon, JK., Tighe, R., et al.[2021]

Nivolumab, a monoclonal antibody that blocks PD-1, shows a 20% overall response rate in patients with metastatic urothelial carcinoma after failing first-line platinum-based chemotherapy, indicating its potential as a treatment option.

While nivolumab is associated with manageable toxicity, serious immune-related adverse events can occur, and current biomarkers like PD-1/PD-L1 expression are not reliable for predicting patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. Raggi, D., Necchi, A., Giannatempo, P.[2019]

In a study of 39 patients with muscle-invasive bladder cancer, the combination of gemcitabine, cisplatin, and the immune checkpoint inhibitor pembrolizumab was effective, achieving pathologic downstaging in 56% of patients and complete pathologic response in 36%.

The treatment was generally safe, with common side effects including thrombocytopenia, anemia, and neutropenia, but no severe immune-related adverse events were reported, indicating a manageable safety profile for this neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. Rose, TL., Harrison, MR., Deal, AM., et al.[2022]

In a phase II trial involving 51 patients with muscle-invasive bladder cancer, the combination of nivolumab and gemcitabine/cisplatin (N+GC) was well tolerated and resulted in a clinical complete response in 59% of patients, indicating its potential effectiveness as a neoadjuvant treatment.

The treatment led to a pathologic complete response in 24% of patients overall and 35% among those who underwent radical cystectomy, suggesting that N+GC can achieve significant tumor reduction before surgery, regardless of the patients' PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. Kim, H., Jeong, BC., Hong, J., et al.[2023]

Recent advancements in immunotherapy, particularly immune-checkpoint inhibitors like atezolizumab and pembrolizumab, have shown significant anti-tumor activity and improved survival rates in patients with advanced urothelial carcinoma who have previously failed platinum-based chemotherapy.

These immune-checkpoint inhibitors have tolerable safety profiles and have been FDA-approved for use in bladder cancer, marking a shift in treatment standards and offering hope for better long-term outcomes compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives. Farina, MS., Lundgren, KT., Bellmunt, J.[2022]

Nivolumab has received accelerated approval from the FDA for treating patients with locally advanced or metastatic urothelial carcinoma who have experienced disease progression after platinum chemotherapy.

This approval marks the second PD-1-targeting therapy approved for bladder cancer within a year, highlighting the growing options for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]

Citations

1. cgoncology.com cgoncology.com/cg-oncology-announces-nature-medicine-publication-of-phase-1b-study-results-evaluating-cretostimogene-grenadenorepvec-in-combination-with-nivolumab-in-muscle-invasive-bladder-cancer/

CG Oncology's Phase 1b Study in Nature Medicine Cretostimogene targets bladder cancer cells, without harming normal cells in the bladder. ... Cretostimogene Grenadenorepvec Data Continues ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39521884/

Oncolytic immunotherapy with nivolumab in muscle-invasive ... These results highlight the potential of this combination regimen to enhance therapeutic efficacy in cisplatin-ineligible patients with muscle-invasive bladder ...

3. urotoday.com urotoday.com/recent-abstracts/urologic-oncology/bladder-cancer/156222-cg-oncology-announces-nature-medicine-publication-of-phase-1b-study-results-evaluating-cretostimogene-grenadenorepvec-in-combination-with-nivolumab-in-muscle-invasive-bladder-cancer.html

CG Oncology Announces Nature Medicine Publication of ... ... Results Evaluating Cretostimogene Grenadenorepvec in Combination with Nivolumab in Muscle-Invasive Bladder Cancer. November 11, 2024. Phase 1b ...

4. urologytimes.com urologytimes.com/view/cretostimogene-grenadenorepvec-plus-nivolumab-shows-promise-in-cisplatin-ineligible-mibc

Cretostimogene grenadenorepvec plus nivolumab shows ... The combination of neoadjuvant cretostimogene grenadenorepvec plus nivolumab was safe and efficacious in patients with cisplatin-ineligible muscle-invasive ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04610671

Study of CG0070 Combined With Nivolumab in Cisplatin ... Early indications of efficacy for the combination treatment include a pathologic complete response rate of 42.1%, which is significantly higher than what has ...

6. cgoncology.com cgoncology.com/cretostimogene-grenadenorepvec-data-continues-to-demonstrate-best-in-class-durability-of-response-as-well-as-consistent-and-compelling-safety-and-efficacy/

Cretostimogene Grenadenorepvec Data Continues to ... 83 out of 110 patients (75.5%) achieved a complete response (CR) at any time in a Phase 3 study of cretostimogene monotherapy for high-risk BCG-unresponsive ...